YOUNG MALE RATS ARE 'DEMASCULINIZED'
AND 'FEMINIZED' BY LOW DOSES OF DIOXIN

Three new studies by researchers at University of Wisconsin
reveal that very low doses of dioxin alter the sexual development
of young male rats, causing demasculinization and
feminization. [1,2,3]

Dr. Linda S. Birnbaum, a scientist with U.S. EPA [Environmental
Protection Agency] calls the new studies "highly significant."[4]
Birnbaum is one of the chief scientists conducting the EPA's
formal reassessment of the toxicity of dioxin (see RHWN #269,
#270, #275). As we reported earlier (RHWN #279), many scientists,
including Birnbaum, now consider dioxin an "environmental
hormone." The new Wisconsin studies support that view.

The Wisconsin researchers, led by Dr. Richard E. Peterson, showed
that dioxin interferes with the sexual development of male rats
exposed to dioxin before, and shortly after, birth. Pregnant
female rats were given a single oral dose of dioxin on the 15th
day of pregnancy; their male offspring showed reduced levels of
male hormones in their blood and a variety of sexual aberrations
that stayed with them as they matured. The young males are
demasculinized and feminized by doses of dioxin too low to cause
any measurable toxicity in the mother rat. The sexual changes in
the young males are both physiological and behavioral, and last
into adulthood.

Dioxin passes through the placenta and enters the fetus, so the
rat fetuses received part of the mother's dose almost
immediately. After birth, the baby rats continued to receive a
small dose of dioxin through their mother's milk. Peterson says
the baby rats received the bulk of their dose through milk. In
rats and humans both, females rid their bodies of dioxin chiefly
by excreting it in their milk. Dioxin is soluble in fats and
oils, and milk is high in fat.

Dioxin is the common name for a family of 75 toxins, the most
potent of which is TCDD [2,3,7,8-tetrachlorodibenzo-P-dioxin].
The Wisconsin researchers used TCDD in their experiments.

Dioxin is not made intentionally for any industrial purpose, but
is produced as a byproduct of the combustion of
chlorine-containing wastes, the bleaching of paper, and the
manufacture of some pesticides. The burning of municipal solid
waste, and of many hazardous wastes, releases dioxin into the
environment, as does paper manufacture. Government officials
responsible for the quality of the environment in the Great Lakes
have called for a phase-out of chlorine, to reduce dioxin levels
in wildlife and humans around the Lakes. (See RHWN #284.)

In the Wisconsin experiments, young males whose mothers were
given as little as 0.064 micrograms of dioxin per kilogram of
body weight showed consistently reduced levels of male hormones,
plus a variety of physical and behavioral changes, including:

--reduced testosterone levels and probably a reduced response to
testosterone. Testosterone is a powerful hormone controlling
various aspects of sexual development in males.

--smaller accessory sex organs, including smaller testicles;

--slower sexual maturation;

--distinctly feminine-style regulation of one hormone related to
testosterone production;

--greater willingness to assume a receptive-female posture when
approached by a sexually stimulated male.

These effects "strongly suggest, though do not conclusively
prove, that TCDD impairs sexual differentiation in the CNS
[central nervous system]," according to Peterson and co-workers.
They go on to say that, "The present study provides the first
evidence that TCDD impairs sexual differentiation of the CNS."
Sexual differentiation--the full development of a female instead
of a male, or vice versa--is affected by hormones circulating in
the blood before and after birth.

Furthermore, these studies "strongly suggest" that "the
demasculinization and feminization caused by IN UTERO and
lactational TCDD exposure are irreversible," the Wisconsin
researchers say. IN UTERO means "in the womb" and lactational
means "from milk."

--The developing male reproductive system is more sensitive to
the effects of this hormone-like toxicant [dioxin] that any other
organ or organ-system studied.

--the unborn or newborn is about 100 times more sensitive to
dioxin than the sexually mature animal.

What do these studies mean for humans?

The Wisconsin researchers speculate, "Thus the findings from this
study raise the possibility that TCDD could potentially affect
sexually dimorphic behavior in man if exposure were to occur
during fetal development." "Sexually dimorphic behavior" refers
to the bodily and behavioral differences between men and women.

Peterson and co-workers point out that male rats typically
inseminate a female rat with up to 10 times as many sperm as are
typically needed to ensure impregnation. Humans, by contrast,
typically release only about as many sperm as would be required
for fertilization. "As a result," Peterson and his co-workers
write, human reductions in sperm production "similar in magnitude
to that in rats would be expected to reduce fertility in man." In
other words, rats can continue to reproduce despite a reduction
in sperm count because they produce an excess of sperm, but
humans do not produce excess sperm so a reduction in human sperm
count would likely reduce humans' ability to reproduce.[5]

"The real question is how general these effects are," Birnbaum
says. Her EPA lab will repeat the Peterson studies with another
strain of rats and eventually other species. And if these effects
occur in another species? "I would get very concerned [about the
potential human-health implications]," Birnbaum told SCIENCE NEWS
reporter Janet Raloff.

At a public hearing on EPA's dioxin reassessment at EPA
headquarters in Washington April 28, a representative of the
American Paper Institute argued that only the study of humans can
reveal anything meaningful about humans. Birnbaum responded
somewhat testily, spelling out a dozen ways in which studies of
rats and mice reveal useful information about dioxin's potential
effects on humans.

June 10 at a Congressional hearing on dioxin in Washington,
Assistant U.S. Surgeon General Barry L. Johnson, announced that a
new study by the National Institute for Occupational Safety and
Health (NIOSH) has found that workers exposed to high levels of
dioxin have abnormally low levels of testosterone (male hormone)
in their blood streams.[6] This finding is consistent with the
rat studies of Peterson and co-workers. We have learned that this
new NIOSH study was presented at a scientific meeting on June 10,
but NIOSH sources have so far not released details of the new
study to the general public.

At the Congressional hearing June 10, under questioning from
Representative Ted Weiss (D-NY), Barry Johnson said that if it
were faced with the Times Beach, Missouri, situation today, the
U.S. Public Health Service would do exactly what it did 10 years
ago, which is to evacuate people from their homes. He said the
Times Beach evacuation was the appropriate response and would be
repeated under similar circumstances today. Another official of
U.S. Public Health Service, Vernon L. Houk, made headlines 14
months ago saying if he had the decision to make over again, he
would not evacuate people from Times Beach. Times Beach is a town
near St. Louis where an unscrupulous waste hauler spread
dioxin-contaminated oil around as a dust suppressant in the
1970s. Horses and other animals became sick and died, and the
Public Health Service evacuated the town in the early 1980s.

During the Congressional hearing Dr. Houk's views were further
contradicted by the testimony of Dr. Marilyn Fingerhut of NIOSH,
who studied the health of 5172 workers exposed to dioxin on the
job. (See RHWN #219.) Dr. Houk made headlines a year ago when he
said that, if dioxin causes cancer in humans at all, it is only
"a weak carcinogen." (See RHWN #249.) Dr. Fingerhut contradicted
this view, reporting that, among workers who had been exposed to
dioxin for at least a year at least 20 years ago, there was 46%
more cancer than among average U.S. males. During the hearing,
Representative Weiss characterized Dr. Houk's views on dioxin as
"quirky" and "cockamamie."
--Peter Montague, Ph.D.